The Radiation Oncology and Surgery Branches of the National Cancer Institute have been involved in prospective randomized studies evaluating the potential role of intraoperative radiotherapy in three major disease sites including resectable and unresectable carcinomas of the pancreas, resectable carcinomas of the stomach, and resectable retroperitoneal sarcomas. We have also been involved in single arm pilot trials involving intraoperative therapy in selected patients with locally advanced tumors not felt likely to be cured by standard therapy such as locally advanced lung carcinomas. To date, 105 patients have been treated with experimental intraoperative radiation therapy on these various protocols and there are an additional 65 other patients being followed as control patients on the various randomized prospective trials. The randomized study in patients with resectable pancreatic carcinoma demonstrates a significant improvement in local control and overall survival. Preliminary evaluation of patients with resectable gastric carcinoma also documents an improvement in local control and an increase in survival, although not statistically significant. In patients with unresectable pancreatic carcinoma and in large resectable retroperitoneal sarcomas, there appears to be no benefit to the use of intraoperative radiation therapy. The trials on pancreas carcinoma and retroperitoneal sarcomas have been closed. Patients are still being accrued for the pilot studies, as well as for the resectable gastric carcinoma study.